Fetal Exposure to Moderate Ethanol Doses: Heightened Operant Responsiveness Elicited by Ethanol‐Related Reinforcers

Abstract

Background Prenatal exposure to moderate ethanol doses during late gestation modifies postnatal ethanol palatability and ingestion. The use of Pavlovian associative procedures, has indicated that these prenatal experiences broaden the range of ethanol doses capable of supporting appetitive conditioning. Recently, a novel operant technique aimed at analyzing neonatal predisposition to gain access to ethanol has been developed. Experiment 1 tested the operant conditioning technique for developing rats described by Arias et al. (2007) and Bordner et al. (2008). In Experiment 2 we analyzed changes in the disposition to gain access to ethanol as a result of moderate prenatal exposure to the drug. Methods In Experiment 1 newborn pups were intraorally cannulated and placed in a supine position that allowed access to a touch-sensitive sensor. Paired pups received an intraoral administration of a given reinforcer (milk or quinine) contingent upon physical contact with the sensor. Yoked controls received similar reinforcers only when Paired pups activated the circuit. In Experiment 2, natural reinforcers (water or milk) as well as ethanol (3% or 6 % v/v) or an ethanol-related reinforcer (sucrose compounded with quinine) were tested. In this Experiment pups had been exposed to water or ethanol (1 or 2 g/kg) during gestational days 17–20. Results Experiment 1 confirmed previous results showing that 1-day-old pups rapidly learn an operant task to gain access to milk, but not to gain access to a bitter tastant. Experiment 2 showed that water and milk were highly reinforcing across prenatal treatments. Furthermore, general activity during training was not affected by prenatal exposure to ethanol. Most importantly, prenatal ethanol exposure facilitated conditioning when the reinforcer was 3% v/v ethanol or a psychophysical equivalent of ethanol’s gustatory properties (sucrose-quinine). Conclusions The present results suggest that late prenatal experience with ethanol changes the predisposition of the newborn to gain access to ethanol-related stimuli. In conjunction with prior literature, this study emphasizes the fact that intrauterine experience with ethanol not only augments ethanol’s palatability and ingestion, but also facilitates the acquisition of response-stimulus associations where the drug acts as an intraoral reinforcer.

Naloxone attenuation of ethanol-reinforced operant responding in infant rats in a re-exposure paradigm

“…As a whole, the present study, in conjunction with recent findings (Bordner et al 2008;March et al 2009;MirandaMorales et al 2010;Pautassi et al 2008b;Ponce et al 2008), strengthens the notion that the developing rat is highly sensitive to appetitive motivational effects of ethanol, as demonstrated through rapid and robust instrumental learning. These effects seem to require a fully functional opioid system.…”

“…Infants also are sensitive to ethanol's appetitive motivational properties, as demonstrated through the use of Pavlovian learning paradigms and primary and second-order conditioning (Molina et al 2007. The use of operant techniques to evaluate the motivational effects of ethanol during early ontogeny has been recently documented in the literature (Bordner et al 2008;March et al 2009;Miranda-Morales et al 2010;Pautassi et al 2008b;Ponce et al 2008). The opioid neurotransmitter system is known to be involved in ethanol reinforcement and intake (Gianoulakis 2009).…”

Endogenous opioids as substrates for ethanol intake in the neonatal rat: The impact of prenatal ethanol exposure on the opioid family in the early postnatal period

“…Consumption of smaller amounts of ethanol during this critical period of development, however, may result in less obvious, yet equally devastating consequences. Recent research suggests that even moderate exposure to ethanol during the last portion of gestation or early postnatal life may enhance ethanol intake [5], [6], [7], [8], [9], [10], and [11], preference [6], [12], and [13], and reinforcement [14], [15], [16], and [17] throughout life. The neurochemical and neuroanatomical mechanisms mediating these effects, however, are currently unknown.…”

“…Brain tissue was collected across several days during early postnatal life (PDs 4, 8 and 12), focusing on ages at which ethanol intake is known to be relatively low, moderate, and high, respectively [30] and [31]. To the extent that ethanol intake is mediated by the endogenous opioid system (e.g., [32], but see [33]) and differs across early ontogeny, and prenatal exposure to the drug alters subsequent consumption (e.g., [5], [6], [7], [8], [9], [10], [11], and [34] and reinforcement [14], [15], [16], and [17] of the drug, we expected to see differences in basal levels of opioid mRNA and/or protein as a function of both ontogeny and prenatal alcohol exposure (PAE). More specifically, we expected to see ontogenetic-dependent upregulation of opioid systems, indicative of ongoing developmental changes within this system.…”

Prenatal alcohol exposure selectively enhances young adult perceived pleasantness of alcohol odors

“…Extensive basic research in animal models demonstrates that prenatal or early neonatal alcohol exposure alters a variety of later behavioral (Abate, et al, 2008; Becker et al, 1993; 1993; Chotro & Arias, 2006; Middleton et al, 2009; March et al, 2009), consummatory (Chotro et al, 2007; Diáz-Cenzano et al, 2014; Miranda-Morales et al, 2014; Shea et al, 2012; Youngentob & Glendinning. 2009), pharmacological (Diáz-Cenzano et al, 2014; Pautassi et al, 2012), biochemical (Middleton et al, 2009), and physiological (Eade et al, 2010; Taylor et al, 1981; Weinberg et al, 1995) responses to alcohol.…”